Tracheal Ultrasound for Diagnosis of Tracheal Cartilaginous Sleeve in Patients with Syndromic Craniosynostosis.

OBJECTIVE: The aim of this study was to assess the utility of ultrasound (US) imaging for diagnosis of abnormal tracheal morphology, such as tracheal cartilaginous sleeves (TCS), in patients with syndromic craniosynostosis (SC). STUDY DESIGN: Age-matched cohort study. SETTING: Tertiary pediatric hospital. METHODS: Two age-matched cohorts were identified: patients with SC and known TCS based upon airway endoscopy and normal controls without tracheal pathology. Enrolled patients underwent awake US of the neck which were randomized and reviewed by blinded pediatric radiologists and rated on presence or absence of normal tracheal cartilage morphology and visualization or nonvisualization of a tracheostomy tube. Fisher's exact test was used to assess pooled data. Fleiss' Kappa (κ) was calculated to assess inter-rater reliability. RESULTS: Ten patients were included in each cohort. Control patients were gender and age-matched to TCS patients with a mean difference of 3.7 months (±3.9 months). Across all raters, cartilage type was correctly identified in 93% (95% confidence interval [CI]: 84%-98%) and tracheostomy visualization in 97% (95% CI: 89%-99%). The sensitivity and specificity for detection of abnormal cartilage pathology was 87% and 100%, respectively. Inter-rater reliability for cartilage assessment was κ = 0.88 (95% CI: 0.67-1.00, P < .05) and 0.83 (95% CI: 0.58-1.00, P < .05) for tracheostomy presence. CONCLUSION: This study demonstrated that tracheal US is a feasible, accurate screening tool for TCS, and can be successfully performed non-sedated in patients up to 18 years of age, both with and without tracheostomy tubes in place.

Surgical management of rare tumors (Part 1).

With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers and the Children's Oncology Group fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g., pleuropulmonary blastoma and desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g., thyroid, melanoma, and gastrointestinal stromal tumor). Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14. This article highlights several of the most common rare tumor types.

Optimizing pediatric tonsillectomy outcomes with an opioid sparing anesthesia protocol: Learning and continuously improving with real-world data.

INTRODUCTION: This quality improvement initiative is a continued pursuit to optimize outcomes by iteratively improving our opioid sparing anesthesia protocol for tonsillectomy with or without adenoidectomy at our pediatric ambulatory surgical center through data driven Plan-Do-Study-Act cycles. METHODS: From 1/2015 through 12/2023, our standardized tonsillectomy protocol underwent nine procedure-specific perioperative Plan-Do-Study-Act cycles, three procedure-specific postoperative prescription Plan-Do-Study-Act cycles, and four general ambulatory surgical center enhanced recovery Plan-Do-Study-Act cycles. We analyzed data from the medical record using statistical process control charts. The primary outcome measure was the percent of patients requiring intravenous opioid in the post anesthesia care unit. Secondary outcomes included maximum post anesthesia care unit pain score, the percent of patients requiring treatment for nausea and/or vomiting in the post anesthesia care unit, and the number of postoperative opioid prescription dosages. Balancing measures were average post anesthesia care unit length of stay, percent of patients with prolonged Post Anesthesia Care Unit length of stay (>120 min), and 30-day reoperation rate. RESULTS: A total of 5654 tonsillectomy with or without adenoidectomy cases were performed at our ambulatory surgical center from 2015 to 2023. The incidence of intravenous opioid administered in the post anesthesia care unit initially rose with opioid free anesthesia launch, but subsequently decreased below the target of 10%. Maximum post anesthesia care unit pain scores rose from mean 3.6 to 4.5, but subsequently returned to the baseline of 3.5, while the incidence of postoperative nausea and/or vomiting improved. The average post anesthesia care unit length of stay increased by 10 min with opioid free anesthesia; however, prolonged post anesthesia care unit stay and 30-day reoperation rates were unchanged. CONCLUSIONS: The continued refinement of our opioid sparing anesthesia protocol has led to reduced perioperative and home opioid use, stable maximum post anesthesia care unit pain scores, and improved postoperative nausea and vomiting rates, with only a slight increase in mean post anesthesia care unit length of stay.

Sex-specific DNA-replication in the early mammalian embryo.

The timing of DNA replication in mammals is crucial for minimizing errors and influenced by genome usage and chromatin states. Replication timing in the newly formed mammalian embryo remains poorly understood. Here, we have investigated replication timing in mouse zygotes and 2-cell embryos, revealing that zygotes lack a conventional replication timing program, which then emerges in 2-cell embryos. This program differs from embryonic stem cells and generally correlates with transcription and genome compartmentalization of both parental genomes. However, consistent and systematic differences existed between the replication timing of the two parental genomes, including considerably later replication of maternal pericentromeric regions compared to paternal counterparts. Moreover, maternal chromatin modified by Polycomb Repressive Complexes in the oocyte, undergoes early replication, despite belonging to the typically late-replicating B-compartment of the genome. This atypical and asynchronous replication of the two parental genomes may advance our understanding of replication stress in early human embryos and trigger strategies to reduce errors and aneuploidies.

An Ancient Disease Hepatosplenic Schistosomiasis.

Schistosomiasis is an ancient disease still affecting more than 200 million people worldwide; calcified Schistosome eggs were discovered in Egyptian mummies (1200-900 BC). A 25-year-old man presented to the emergency department with heartburn. He immigrated to the United States from Sub-Saharan Africa. His physical exam revealed hepatosplenomegaly, and he was eventually diagnosed with Schistosomiasis.

Pediatric Salivary Gland Pathology.

Benign and malignant salivary gland disorders are uncommon in the pediatric population; however, these can be frequently seen in pediatric otolaryngology or oral and maxillofacial surgery practices. The astute clinician should be aware of the clinical presentation, diagnosis, and management options for common inflammatory, infectious, benign, and malignant disorders of salivary glands.

Injection Medialization in Infants with Vocal Fold Immobility Improves Dysphagia.

BACKGROUND: Unilateral vocal fold immobility (VFI) is a known cause of morbidity amongst children following congenital heart surgery. Injection medialization (IM) provides medial distraction and improves glottic closure. Limited objective data is available for the effect of IM in young children (<2 years-old) with VFI. METHODS: Retrospective case series of infants <2 who underwent IM for VFI after congenital cardiac surgery. Primary outcome was objective reduced risk of aspiration based on Dysphagia and Outcome Severity Scores (DOSS) on Video swallow study (VFSS) performed prior to and within 4 weeks following IM. Secondary analysis included perioperative complications and number of children who were able to avoid NG or G tube placement. RESULTS: 17 children <2 years of age had unilateral VFI after congenital cardiac surgery and underwent IM. The median age at time of initial cardiac surgery was 6 days (IQR 3-7). There was no intraoperative or postoperative stridor or associated complications. All 17 patients had preoperative aspiration noted on VFSS. Average swallowing outcomes on VFSS improved after IM with an increase in DOSS score (preop score 3 (IQR 2-4) to postop score 6.5 (IQR 5-7) [P = 0.001]). At 2 months following IM, of the patients who had improvement in swallowing function, 50% (n = 6) were able to feed completely orally, 25% (n = 3) were fed orally with an NG wean, and 3 (25%) had a G tube placed. CONCLUSION: Initial results suggest that IM is safe and improves early objective swallowing outcomes in children <2 years old with VFI after congenital cardiac surgery. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

Multidisciplinary Advanced Surgical Planning for Slide Tracheoplasty Using 3D-Printed Models.

OBJECTIVE: The objective of this study was to develop and assess multidisciplinary advanced surgical planning (ASP) sessions using three dimensional (3D) printed models for cervicothoracic slide tracheoplasty (CST). We hypothesized that these sessions would improve surgeon confidence, streamline intraoperative planning, and highlight the utility of 3D modeling. METHODS: 3D-printed patient-specific trachea models were used in pre-operative ASP sessions consisting of a multidisciplinary case discussion and hands-on slide tracheoplasty simulation. Participants completed a survey rating realism, utility, impact on the final surgical plan, and pre- and post-session confidence. Statistical analysis was performed via Wilcoxon and Kruskal-Wallis tests. RESULTS: Forty-eight surveys were collected across nine sessions and 27 different physicians. On a 5-point Likert scale, models were rated as "very realistic", "very useful" (both median of 4, IQR 3-4 and 4-5, respectively). Overall confidence increased by 1.4 points (+/- 0.7, p < 0.0001), with the largest change seen in those with minimal prior slide tracheoplasty experience (p = 0.005). Participants felt that the sessions "strongly" impacted their surgical plan or anticipated performance (median 4, IQR 4-5), regardless of training level or experience. CONCLUSION: 3D-printed patient-specific models were successfully implemented in ASP sessions for CST. Models were deemed very realistic and very useful by surgeons across multiple specialties and training levels. Surgical planning sessions also strongly impacted the final surgical plan and increased surgeon confidence for CST. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3395-3401, 2024.

Epigenetic aging of human blood cells is influenced by the age of the host body.

Allogenic hematopoietic stem cell transplantation is a therapeutic procedure performed over a wide range of donor and recipient age combinations, representing natural experiments of how the age of the recipient affects aging in transplanted donor cells in vivo. We measured DNA methylation and epigenetic aging in donors and recipients and found that biological epigenetic clocks are accelerated in cells transplanted into an older body and decelerated in a younger body. This is the first evidence that the age of the circulating environment influences human epigenetic aging in vivo.

Surface Reconstruction of the Pediatric Larynx via Structure from Motion Photogrammetry: A Pilot Study.

Endoscopy is the gold standard for characterizing pediatric airway disorders, however, it is limited for quantitative analysis due to lack of three-dimensional (3D) vision and poor stereotactic depth perception. We utilize structure from motion (SfM) photogrammetry, to reconstruct 3D surfaces of pathologic and healthy pediatric larynges from monocular two-dimensional (2D) endoscopy. Models of pediatric subglottic stenosis were 3D printed and airway endoscopies were simulated. 3D surfaces were successfully reconstructed from endoscopic videos of all models using an SfM analysis toolkit. Average subglottic surface error between SfM reconstructed surfaces and 3D printed models was 0.65 mm as measured by Modified Hausdorff Distance. Average volumetric similarity between SfM surfaces and printed models was 0.82 as measured by Jaccard Index. SfM can be used to accurately reconstruct 3D surface renderings of the larynx from 2D endoscopy video. This technique has immense potential for use in quantitative analysis of airway geometry and virtual surgical planning.

Preoperative Imaging and Surgical Findings in Pediatric Frontonasal Dermoids.

OBJECTIVE: To review cases of congenital frontonasal dermoids to gain insight into the accuracy of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) in predicting intracranial extension. METHODS: This retrospective study included all patients who underwent primary excision of frontonasal dermoids at an academic children's hospital over a 23-year period. Preoperative presentation, imaging, and operative findings were reviewed. Receiver operating characteristic (ROC) statistics were generated to determine CT and MRI accuracy in detecting intracranial extension. RESULTS: Search queries yielded 129 patients who underwent surgical removal of frontonasal dermoids over the study period with an average age of presentation of 12 months. Preoperative imaging was performed on 122 patients, with 19 patients receiving both CT and MRI. CT and MRI were concordant in the prediction of intracranial extension in 18 out of 19 patients. Intraoperatively, intracranial extension requiring craniotomy was seen in 11 patients (8.5%). CT was 87.5% sensitive and 97.4% specific for predicting intracranial extension with an ROC of 0.925 (95% CI [0.801, 1]), whereas MRI was 60.0% sensitive and 97.8% specific with an ROC of 0.789 (95% CI [0.627, 0.950]). CONCLUSION: This is the largest case series in the literature describing a single institution's experience with frontonasal dermoids. Intracranial extension is rare and few patients required craniotomy in our series. CT and MRI have comparable accuracy at detecting intracranial extension. Single-modality imaging is recommended preoperatively in the absence of other clinical indications. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1961-1966, 2024.

Ultrasound Screening After Cardiac Surgery Shows Vocal Fold Impairment and Predicts Aspiration.

INTRODUCTION: Vocal fold motion impairment (VFMI) is a known consequence after high-risk cardiac surgery. We implemented a universal laryngeal ultrasound (LUS) screening protocol for VFMI after the Norwood and aortic arch surgery. We hypothesized that LUS would accurately identify VFMI and predict postoperative aspiration. METHODS: We implemented a screening algorithm with LUS for patients undergoing high-risk cardiac surgery at a tertiary care pediatric hospital. Positively screened patients underwent flexible nasolaryngoscopy (FNL). Patients with an abnormal FNL underwent a video-fluoroscopic swallow study (VFSS). Patient demographics, length of stay, and swallowing outcomes were assessed. Two-tailed chi square and Wilcoxon rank sum tests were used to assess for differences. RESULTS: Sixty-seven patients underwent either Norwood or arch reconstruction over a 16-month period and underwent universal LUS. The average birth weight was 3.24 kg (SD 0.57). Of the 67 patients, VFMI was identified by LUS and 100% confirmed on FNL in 58.21% (n = 39/67) of patients. Aspiration and penetration on VFSS were higher in the group with VFMI as compared with those without VFMI (53.8% vs. 21.4%, p = 0.008). There was no difference in length of stay between patients who did not have a diagnosis of VFMI and those found to have VFMI (41.0 days vs 45.3 days p = 0.73). CONCLUSIONS: Universal LUS screening for patients following high-risk cardiac surgery may lead to earlier identification of postoperative VFMI and aspiration. Recognition of VFMI through this universal screening program could lead to earlier interventions and possibly improved swallowing outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1939-1944, 2024.

Reducing Pediatric Posttonsillectomy Opioid Prescribing: A Quality Improvement Initiative.

OBJECTIVE: Postoperative pain is the most common morbidity associated with tonsillectomy. Opioids are frequently used in multimodal posttonsillectomy analgesia regimens; however, concerns regarding respiratory depression, drug-drug interactions, and medication misuse necessitate responsible opioid stewardship among prescribing surgeons. It is unclear if intentionally reducing opioid prescription doses negatively affects the patient experience. METHODS: A quality improvement team reviewed all posttonsillectomy opioid prescriptions at a pediatric ambulatory surgery center between January and June 2021 (preintervention, 163 patients). Following this review, we performed an opioid education session for surgeons and studied opioid prescribing habits between July and December 2021 (Plan-Do-Study-Act [PDSA] 1, 152 patients). We then implemented a standardized prescription protocol of 7 doses of oxycodone per patient and again reviewed prescriptions between January and June 2022 (PDSA 2, 178 patients). The following measures were evaluated: initial number of opioid doses prescribed, need for refills, 7-day emergency department (ED) visits, and readmissions. RESULTS: Each intervention reduced the average number of initial oxycodone doses per patient (12.2 vs 9.2 vs 6.9 doses, P < .001). There were no changes in the rate of refill requests, 7-day ED visits, and readmissions, by descriptive or Statistical Process Control analyses. DISCUSSION: In 2 PDSA cycles, we achieved a 43% reduction in the number of doses of oxycodone prescribed following tonsillectomy. We did not observe any increased rates in balancing measures, which are surrogates for unintentional effects of PDSA changes, including refills, ED presentations, and readmission rates. IMPLICATIONS FOR PRACTICE: Directed provider education and standardized posttonsillectomy prescription protocols can safely decrease postoperative opioid prescribing. Further PDSA cycles are required to consider even fewer opioid prescription doses.

Impact of Ketorolac on Reoperation for Hemorrhage After Pediatric Tonsillectomy: A Single-Center Retrospective Propensity-Matched Study.

OBJECTIVE: To determine if perioperative ketorolac is associated with an increased rate of reoperation for hemorrhage after pediatric tonsillectomy at 30 days and 48 hours. STUDY DESIGN: Single-center retrospective propensity-matched study. SETTING: Quaternary pediatric hospital and ambulatory surgery center. METHODS: Patients less than 18 years old undergoing tonsillectomy or adenotonsillectomy between January 1, 2015 and October 1, 2020 were included. Hemorrhage rates between exposed (K+) and unexposed (K-) patients were calculated for the total cohort and a 1:1 propensity-matched cohort. Additional analyses included: multivariable logistic regression, subgroup analysis of ASA 1 and 2 patients, subgroup analysis comparing children with teenagers. RESULTS: There were 5873 patients (42.1% K+) in the full cohort and 4694 patients in the propensity-matched cohort. Reoperation for hemorrhage within 30 days occurred in 1.9% of K+ patients and 1.6% of K- patients (P = 0.455) in the full cohort and 1.9% of K+ patients and 1.7% of K- patients (odds ratio [OR] 1.10, 95% confidence interval [CI] 0.72-1.69, P = 0.662) in the propensity-matched cohort. Reoperation within 48 hours occurred in 0.65% of K+ patients and 0.53% of K- patients (P = 0.679) in the full cohort and 0.68% of K+ patients and 0.51% of K- patients (OR 1.33, 95% CI 0.63-2.81, P = 0.451) in the propensity-matched cohort. There was no association between perioperative ketorolac administration and reoperation for hemorrhage in any of the other analyses. CONCLUSION: Ketorolac at end of surgery should be considered as part of the nonopioid analgesic regimen for pediatric tonsillectomy.

Single-cell m6A mapping in vivo using picoMeRIP-seq.

Current N6-methyladenosine (m6A) mapping methods need large amounts of RNA or are limited to cultured cells. Through optimized sample recovery and signal-to-noise ratio, we developed picogram-scale m6A RNA immunoprecipitation and sequencing (picoMeRIP-seq) for studying m6A in vivo in single cells and scarce cell types using standard laboratory equipment. We benchmark m6A mapping on titrations of poly(A) RNA and embryonic stem cells and in single zebrafish zygotes, mouse oocytes and embryos.

Surgery for Velopharyngeal Insufficiency Following Cleft Palate Repair: An Audit of Contemporary Practice and Proposed Schema of Techniques and Variations.

OBJECTIVE: Surgical treatment of velopharyngeal insufficiency (VPI) includes a wide array of procedures. The purpose of this study was to develop a classification for VPI procedures and to describe variations in how they are performed.Design/participants/setting/outcomes: We completed an in-depth review of the literature to develop a preliminary schema that encompassed existing VPI procedures. Forty-one cleft surgeons from twelve hospitals across the USA and Canada reviewed the schema and either confirmed that it encompassed all VPI procedures they performed or requested additions. Two surgeons then observed the conduct of the procedures by surgeons at each hospital. Standardized reports were completed with each visit to further explore the literature, refine the schema, and delineate the common and unique aspects of each surgeon's technique. RESULTS: Procedures were divided into three groups: palate-based surgery; pharynx-based surgery; and augmentation. Palate-based operations included straight line mucosal incision with intravelar veloplasty, double-opposing Z-plasty, and palate lengthening with buccal myomucosal flaps. Many surgeons blended maneuvers from these three techniques, so a more descriptive schema was developed classifying the maneuvers employed on the oral mucosa, nasal mucosa, and muscle. Pharynx-based surgery included pharyngeal flap and sphincter pharyngoplasty, with variations in design for each. Augmentation procedures included palate and posterior wall augmentation. CONCLUSIONS: A comprehensive schema for VPI procedures was developed incorporating intentional adaptations in technique. There was substantial variation amongst surgeons in how each procedure was performed. The schema may enable more specific evaluations of surgical outcomes and exploration of the mechanisms through which these procedures improve speech.

The RNA m6A landscape of mouse oocytes and preimplantation embryos.

Despite the significance of N6-methyladenosine (m6A) in gene regulation, the requirement for large amounts of RNA has hindered m6A profiling in mammalian early embryos. Here we apply low-input methyl RNA immunoprecipitation and sequencing to map m6A in mouse oocytes and preimplantation embryos. We define the landscape of m6A during the maternal-to-zygotic transition, including stage-specifically expressed transcription factors essential for cell fate determination. Both the maternally inherited transcripts to be degraded post fertilization and the zygotically activated genes during zygotic genome activation are widely marked by m6A. In contrast to m6A-marked zygotic ally-activated genes, m6A-marked maternally inherited transcripts have a higher tendency to be targeted by microRNAs. Moreover, RNAs derived from retrotransposons, such as MTA that is maternally expressed and MERVL that is transcriptionally activated at the two-cell stage, are largely marked by m6A. Our results provide a foundation for future studies exploring the regulatory roles of m6A in mammalian early embryonic development.

Tracheal Mirror Image Artifact in Patients With Normal and Pathologic Tracheas.

Ultrasonography is gaining popularity as a diagnostic imaging modality for airway pathology. Tracheal ultrasound (US) has several nuances that are important for clinicians, including imaging artifacts, which can be mistaken for pathology. Tracheal mirror image artifacts (TMIAs) occur when the US beam is reflected back to the transducer in a nonliner direction or with multiple timesteps. It has previously been believed that the convexity of the tracheal cartilage prevents mirror image artifacts, but in reality, the air column acts as an acoustic mirror and causes TMIA. We describe a cohort of patients with both normal and pathologic tracheas, all of whom have TMIA on the tracheal US. These artifacts are important to recognize, especially as the airway US becomes more commonplace.